Our work demonstrated that salivary gland extracts from different species of blood-sucking leeches dramatically inhibit lung tumor colonization produced by intravenous injection of a variety of syngeneic murine tumors. To study the mechanism of this effect, isolate the active principal(s), and elucidate its biochemical nature, we intend: (1)\to isolate the active principal(s) from the extract responsible for the inhibitory effect lung colonization by intravenously injected t241 sarcoma cells; (2)\to assay in vivo representative biochemical fractions for their capacity to clear tumor cells from the lung (which is an index of antimetastatic activity); and (3)\to characterize and evaluate further the ability of the active fractions to inhibit hemostasis, block proteolytic or glycosidic enzymes secreted by tumor cells, and arrest tumor cell invasion in chemotactic artificial chambers. This study will require the use of several different methods and techniques including: (1)\platelet aggregation and coaggulation techniques; (2)\tissue culture; (3)\labeling of tumor cells and organ, blood, and urine radioactivity monitoring in vivo; (4)\purification of tumor cells by centrifugal elutriation; (5)\induction of experimental metastases; (6)\biochemical fractionation of proteins; and (7)\testing of purified biochemical fractions for their biological activity in vivo and in vitro and their capacity to inhibit enzymes in biochemical reactions. (J)